Routine diagnosis of respiratory virus infections caused by type A and B influenza, para-influenza, respiratory synctial, and adenoviruses has been encumbered by relatively slow tissue culture methodology. Detection and identification of viral antigen directly in clinical specimens, without prior cultivation in cell culture, would provide a means of rapid viral diagnosis. Methods capable of this are electron microscopy, immunofluorescent (IF) or immunoperoxidase (IP) staining of cells from the site of infection, radio-immunoassay, and enzymeimmunoassay (EIA). For reasons of safety, simplicity, and versatility we are focusing on EIA methods. Most EIA's bind an enzyme label to specific antibody by covalent linkage. To increase sensitivity, we propose using liposomes which can entrap various enzymes in the aqueous compartment between lipid bilayers during their formation as the label. Liposomes can be made antigen specific (targeted) by covalent linkage of specific antibody to the surface of the liposome. After binding to specific antigen, enzymatic activity can be released by detergent lysis. We will develop a targeted liposome EIA and optimize that assay to detect 30 TCID50 of influenza A(H1N1). Comparable assays for influenza A (H3N2), influenza B, respiratory syncytial virus, parainfluenza virus types 1, 2, and 3, and the adenovirus group will be developed. Preliminary testing will involve tissue culture pools of virus. Final testing with clinical specimens will compare the EIA method with standard tissue culture methods. The eventual goal of this research is to develop diagnostic methods that will supply physicians with etiologic information rapidly enough to influence patient care.